Three prolactin receptor isoforms were isolated from the purified ovarian receptor, indicating structural heterogeneity of receptors possibly derived from the same gene. HPLC analysis and DEAE chromatography demonstrated three distinct ovarian lactogen receptor species with unique and highly reproducible retention times which migrated as single bands of 80, 40 and 34 kDa on SDS-PAGE. Subsequent studies demonstrated that these were not associated with thiol linkages. Immunological studies indicated homology among the three ovarian receptor forms and the rat liver receptor, and also demonstrated that the 80 kDa ovarian species contains an amino acid sequence that is not present in the 34 kDa and 40 kDa species or the rat liver receptor. The latter finding, coupled to the demonstration of a single 80 kDa protein species under reducing conditions, conclusively demonstrated that the 80 kDa form is not a dimer of the 34 kDa and 40 kDa species. This was also observed at the molecular level with the isolation and characterization of novel ovarian cDNA clones coding for distinct receptor isoforms. One of these is a membrane-anchored receptor bearing an extended and unique cytoplasmic domain with the potential for signal transduction and mitogenic activity. Another is a truncated receptor with a short cytoplasmic domain possibly involved in transport and/or clearance, and a third codes for a low Mr binding site capable for expression as a soluble protein. Recent studies have demonstrated that the LH receptor gene contains several introns, located within the region coding for the extracellular domain of the molecule, which determine the nature and generation of LH receptor isoforms. By the isolation of a rat testicular cDNA clone (of deduced amino acid sequence lacking the transmembrane) followed by the expression of this cDNA as a soluble protein in COS 1 cells it was demonstrated that the N- terminal extracellular regions of the LH receptor plays a major role in gonadotropin binding. These findings are of great interest because they demonstrate that the LH receptor is distinct from most other G-protein-coupled receptors, which are intronless and contain their binding domains within the transmembrane region rather than the extracellular domain. In other studies correlation between changes of LH receptor number and steady state levels of LH receptor mRNAs (5.8, 2.6 and 2.3 kb) have demonstrated that the expression of LH receptors induced during follicular maturation, ovulation and desensitization is related to prevailing levels of LH receptor mRNA in the ovary.